[Perineal approach to repair rectal and cutaneous fistulas involving the urethra and bladder]. / Perinealer Zugang zur Korrektur von rektalen und kutanen Fisteln zu Urethra und Blase.

The perineal approach was used in ten patients for the repair of fistulas involving the bladder or prostatic urethra. In the case of radiotherapy-induced (n=2) or recurrent fistulas (n=4) fecal diversion and interposition of the gracilis muscle was performed. In addition in three patients prostatectomy was performed. All fistulas were repaired successfully with minimal morbidity.

Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

[Lymphadenectomy for penile cancer. Diagnostic and prognostic significance as well as therapeutic benefit]. / Lymphadenektomie beim Peniskarzinom. Diagnostische und prognostische Bedeutung sowie therapeutischer Nutzen.

Lymphadenectomy is an essential part of diagnosis and treatment of the squamous cell carcinoma of the penis. Lymphadenectomy is performed depending on various characteristics of penile cancer such as depth of invasion, tumor grade, invasion into the corpora cavernosa, invasion into vascular and lymphatic vessels. In case the inguinal lymphnodes are not palpable a modified lymphadenectomy is indicated. The limits of lymphadenectomy are extended to the radical type of dissection when the frozen section indicates cancer. Inguinal lymphadenectomy is always performed on both sides. Are more than 2 nodes positive the lymphnodes in the true pelvis have to be resected as well. The dynamic sentinel lymphnode dissection may replace the modified approach in case randomized prospective studies will confirm the initial positive results and morbidity can be reduced as well. The immediate lymphadenectomy is superior to the delayed lymphadenectomy (palpable nodes during followup) in terms of local recurrence and survival. According to the risk profile patients with palpable inguinal lymphnodes can be initially managed conservatively. In case the lymphnodes remain palpable, lymphadenectomy is indicated. In this situation it is reasonable to perform imaging studies of the pelvis and abdomen for adequate planning of the surgical approach. Neoadjuvant chemotherapy is reasonable for patients with bulky nodes fixed to the skin or fascia because this improves respectability, freedom from local recurrence and increases survival. Adjuvant chemo- and/or radio-therapy are reserved for extended disease or palliative situations.

Effects of telencephalic ablation on visual unit, sustained potential shift, and EEGs recorded from the toad tectum in response to a visual stimulus.

Extracellular recordings were made of visual unit activity, sustained potential shifts (SPSs), and electroencephalographic activity (EEGs) from the optic tectum and of EEGs from the telencephalon of immobilized toads (Bufo bufo). Moving visual stimuli were presented, and the bioelectric responses were monitored both before and after ligature of the telencephalon. The operation reduced the neuronal spike frequency and the amplitude of the tectal SPS and EEG responses. EEGs were still recorded from the tectum and even the isolated telencephalon. The results are discussed in relation to possible adaptive functions of SPS and EEG changes, the genesis of the EEG, and the role of the telencephalon in visually guided prey-catching behavior.

Miniature three-function transmitting system for single neuron recording, wireless brain stimulation and marking.

A telemetric micro-transmitting system has been developed for extracellular single unit recording, electrical brain stimulation and marking of the recording and stimulation site in small freely moving animals. The action potentials are transmitted by using frequency modulation for distances up to 10 m. Electrical brain stimulation through the recording electrodes is performed by means of an inductively powered circuit which is combined with the transmitter (mass of the system 2.38 g). Biphasic current pulses can be applied. Pulse frequency and duration are wireless remotely controlled. The recording and stimulation site in the brain can be marked by means of iron deposits.

Visual unit, EEG and sustained potential shift responses in the brains of toads (Bufo bufo) during alert and defensive behavior.

Cranially mounted differential preamplifiers allowed visual unit activity, EEGs and sustained potential shifts to be monitored from the tectum of freely moving toads (Bufo bufo). Alert behavior was elicited by a moving visual stimulus. Movement of the stimulus in the receptive field of a unit elicited its activity and increased the amplitude of the high frequency component of the local EEG, accompanied by a sustained potential shift. When an animal received a "prod" with a perspex rod, defensive behavior ensued accompanied by slight activity of the visual unit, a large increase in the amplitude of the lower frequency component of the EEG and a large, sustained, potential shift. The results are discussed in relation to the specific neuronal unit responses of the animal and to possible sensitising functions of the non-specific EEG and sustained potential shift responses.

Altered prostate specific antigen reference range after transurethral resection of the prostate.

OBJECTIVES: We investigated how transurethral resection of the prostate (TURP) affected the serum concentration of prostate specific antigen (PSA) and whether the reference range for PSA has to be altered in these patients following TURP. METHODS: 55 patients were retrospectively analysed. All had undergone TURP for bladder outlet obstruction due to benign prostatic hyperplasia which was confirmed by histopathological amination. PSA was determined pre-operatively and postoperatively every 6 months for 48 months. These patients were compared to 12 patients who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP). In the latter group, in all patients a TURP had been performed up to 7 years before CaP was diagnosed. RESULTS: The median PSA concentration was 4.9 ng/ml before TURP and was subsequently reduced to 0.6 ng/ml after 48 months. There was a steady decrease of the PSA concentration during the observation period. In contrast in patients who subsequently developed a CaP, the median PSA concentration before TURP was 6.8 ng/ml and was reduced to only 2.2 ng/ml after 48 months. PSA levels started to rise before CaP was diagnosed. CONCLUSION: After a TURP with a benign histopathologic specimer) PSA levels decrease steadily to values below 2 ng/ml. In case these patients demonstrate a rising PSA in the follow-up after partial prostatectomy, a CaP should be ruled out.

Are age-specific reference ranges for prostate specific antigen population specific?

INTRODUCTION: At present PSA is Considered to be the leading screening test for prostate cancer. We determined whether in men 60 to 79 year old with a serum prostate specific antigen (PSA) within age specific PSA reference ranges prostate biopsy could be safely eliminated. METHODS: We retrospectively analysed all 60-79 year old men who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP) at our institution. All patients had undergone prostate biopsy following an abnormal rectal examination and/or PSA greater than 4.0 ng/ml. We compared our results using the standard reference range of 0 to 4.0 ng/ml with those we had obtained using the age specific PSA reference ranges of Oesterling et al. RESULTS: 204 men between 60-69 years and 67 men between 70-76 years had undergone RPP for CaP. Applying age specific PSA reference ranges 56 CaP would have been overlooked. Of those 46% had a favourable histology. Taken together 54% of the cancers overlooked had an unfavourable histology. CONCLUSION: In contrast to previous reports of unfavourable histological characteristics in only 5-24% of missed cancers, applying age specific PSA reference ranges, 54% of missed cancers in our patients exhibited an unfavourable histology. We therefore conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population.

Tissue polypeptide specific antigen serum concentrations in patients with newly diagnosed prostatic diseases.

UNLABELLED: Recently, tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). In our study we investigated the ability of the TPS serum concentration as a staging marker in patients with newly diagnosed CaP. METHODS: Serum levels of TPS and PSA were determined in patients with newly diagnosed, untreated CaP (pT1-3pNoMo: n = 71; T1-4NxM+: n = 39) and BPH (n = 30). The TPS serum concentration was correlated to the PSA serum concentration. RESULTS: Median TPS concentration was 33.6 U/L in the pT1-3pNoMo-group; 113.5 U/L in the Tl-4NxM(+)-group and 59.7 U/L in the BPH-group. Although the TPS concentration failed to discriminate between patients with localized CaP and BPH, it discriminated very well between patients with (M+) and without (Mo) bone metastases (p < 0.001). Furthermore no correlation with PSA levels could be established. CONCLUSION: The TPS serum concentration seems to provide additional information in the initial staging of patients with newly diagnosed untreated CaP.

Serum levels of prostate specific antigen in men on hemodialysis.

UNLABELLED: The measurement of prostate specific antigen (PSA) is widely used for the early detection of prostate cancer. However the influence of renal failure on the serum levels of the PSA molecular forms is still a matter of investigation. We therefore examined the serum concentration of total and free PSA in patients undergoing hemodialysis and discuss the influence of renal failure on both types. MATERIALS AND METHODS: Serum concentrations of total PSA, free PSA and the free-to-total PSA ratio were measured in 48 men undergoing hemodialysis. Total and free PSA levels were measured employing a chemiluminescent enzyme immunoassay. RESULTS: Serum levels of total PSA, free PSA as well as the free-to-total PSA ratio did not change significantly in uremic patients after hemodialysis. Median total PSA concentration was 1.1 ng/mL before and 1.15 ng/mL after hemodialysis (p = 0.24); median free PSA concentration was 0.29 ng/mL before and 0.32 ng/mL after hemodialysis (p = 0.14). Median free-to-total PSA ratio was 0.29 ng/mL before and 0.31 ng/mL after hemodialysis (p = 0.66). CONCLUSION: Serum free PSA as well as total PSA is not eliminated by hemodialysis and the slightly elevated levels of free PSA and the free-to-total PSA ratio in uremic patients after hemodialysis may be caused by the concomitant decrease in binding proteins. We therefore conclude that the reference ranges for total PSA, free PSA and the f-/t-PSA ratio are applicable undergoing chronic hemodialysis.

Age related changes of free and total prostate specific antigen in serum.

UNLABELLED: PSA in serum exists in several molecular forms. The amount of free and total PSA and ratio are discussed to be useful to increase the ability of PSA to distinguish prostate cancer from benign prostatic hyperplasia. Therefore, we tried to characterize the age related changes of free and total PSA in a German rural population. METHODS: Serum samples were obtained from 697 men. All study participants were between 20 and 79 years old and had no clinical evidence of prostate cancer by serum PSA, digital rectal examination and transrectal ultrasonography. The sera were kept frozen at -20 degrees C until analysis and were assayed within 3 months after sampling. Free and total PSA values were determined employing a chemiluminescent enzyme immunoassay (Immulite PSA and Freies PSA, DPC Biermann). RESULTS: Free PSA, total PSA and the free-to-total PSA ratio (f-/t-ratio) demonstrated a correlation with patient age (r = 0.855, p = 0.0141; r = 0.857, p = 0.0137; r = -0.788, p = 0.0352). Employing the median and the 95% percentile the age-specific reference ranges for free and total PSA were calculated. For the f-/t-ratio the median and the interquartile range (i.e. 25th-75th percentile) were calculated. CONCLUSION: In confirmation of a recent report, we found a direct correlation of free PSA, total PSA and the f-/t-ratio with age, whereas free and total PSA increases, the f-/t-ratio decreased with advancing age.

Cytokeratin markers in patients with prostatic diseases.

OBJECTIVES: Recently tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes both cytokeratin 8 and 18 fragments, is thought to improve sensitivity and specificity of TPS. In our study we investigated the ability of the TPS and cyfra 8/18 serum concentration to discriminate between patients with clinically localized CaP and BPH. METHODS: Serum levels of TPS and Cyfra 8/18 were determined in patients with untreated CaP (pT1-3pNoMo: n = 11) and BPH (n = 22). The TPS and the Cyfra 8/18 concentrations were correlated to the prostate specific antigen (PSA) serum concentration. RESULTS: Median TPS concentration was 45.3 U/L in CaP-patients and 54.8 U/L in BPH-patients. This difference is statistically not significant (p = 0.2). Median Cyfra 8/18 level was 0.64 ng/mL in CaP-patients and 0.57 ng/mL in BPH-patients. This difference is statistically not significant (p = 0.91). Furthermore no correlation with PSA levels could be established (TPS: r = -0.13; Cyfra 8/18: r = 0.17). CONCLUSION: In contrast to recent reports we found both cytokeratin markers, TPS as well as Cyfra 8/18, to be non-discriminative parameters in CaP and BPH.

Serum concentrations of transforming growth factor-beta 1 in patients with benign and malignant prostatic diseases.

INTRODUCTION: Transforming growth factor-beta 1 (TGF-beta 1) is found to be most markedly elevated in prostate cancer tissue. We determined the concentration of serum TGF-beta 1 in patients with cancer of the prostate (CaP), and correlated them to tumour stage and serum PSA. METHODS: Serum TFG-beta 1 levels and serum PSA levels were determined in 80 patients with untreated CaP (Group I: pT1-3pNoMo: n = 58; Group II: T1-3pN + Mo: n = 6; Group III: T1-4NxM+: n = 16). Patients with histologically confirmed BPH (n = 50) served as controls. RESULTS: Median TGF-beta 1 levels were not different in CaP- and in BPH-patients (32.86 ng/ml and 35.15 ng/ml respectively; p > 0.05). Furthermore there was no increase in TGF-beta 1 concentrations with advancing tumour stage (Group I: 32.86 ng/ml; Group II: 34.3 ng/ml; Group III: 33.44 (ng/ml; p > 0.05). No correlation with PSA levels could be established (Spearman r = -0.19; p = 0.05). CONCLUSION: TGF-beta 1 was found to be non-discriminative between BPH and CaP. Furthermore no TGF-beta 1 increase could be observed with advancing tumour stage in patients with CaP.

Critical aspects related to the interpretation of the free-to-total PSA-ratio.

INTRODUCTION: The number of assays available for the measurement of total and free PSA is increasing. As different methods can determine different PSA concentrations as well as different free-to-total PSA ratios in identical serum samples, the cut-offvalue for the ratio still needs to be determined. METHODS: 114 sera from patients with histologically confirmed benign prostatic hyperplasia (BPH; n = 58) and cancer of the prostate (CaP; n = 56) were analyzed with two different assays. Free PSA (free), total PSA (total) and the free-to-total- PSA ratio (ratio) were determined employing Enzym-Test PSA und freies PSA (Boehringer Mannheim, Germany) and Immulite PSA und freies PSA (DPC Biermann, Bad Nauheim, Germany) RESULTS: The statistical results are tabulated below: [table: see text] CONCLUSION: Direct comparison of the two assays revealed a high statistical correlation (r = 0.94-0.99) for free and total PSA. In contrast, the ratio of the two assays was not as reproducible (r = 0.81-0.83). This result indicates that the reference range for the ratio is dependent on the assay employed and an that uncritical use of an applied reference range can be counter-productive.

Metastatic workup of patients with prostate cancer employing alkaline phosphatase and skeletal alkaline phosphatase.

PURPOSE: To compare the efficacy of two tests, alkaline phosphatase (AP) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bone metastases (M+) from those without bone metastases (Mo). MATERIALS AND METHODS: Patients with previously untreated CaP were entered in the retrospective analysis. Serum concentrations of AP (n = 215) and SAP (n = 73) were available. After staging the patients could be divided into 2 groups: Group I: patients with CaP and bone metastases (cT2-4 NxMoss AP: n = 40; SAP: n = 21) Group II: patients with CaP without bone metastases (cT3-4 Nx Mo; pT1-3 No Mo; AP: n = 175; SAP: n = 52). RESULTS: None of the Mo patients but 71% of the M+ patients exhibited a SAP value above the reference range (< 19 ng/ml). This difference is statistically significant (p < 0.001) and resulted in a sensitivity and specificity of 71% and 100%, respectively. The Youden-index is 0.7. In contrast 7% of the Mo patients and only 13% of the M+ patients exhibited a AP value above the reference range (< 170 U/l). This difference is statistically not significant (p = 0.71) and resulted in a sensitivity and specificity of 13% and 93%, respectively. The Youden-index is 0.06. CONCLUSION: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides more information than AP concerning the skeletal status of these patients.

Multi-slice CT urography after diuretic injection: initial results.

PURPOSE: To investigate the feasibility of CT urography (CTU) using a multi-slice (MS) scanner and to find out whether a low-dose diuretic injection is advantageous for the opacification of the urinary tract. METHODS: MS-CTU was performed in 21 patients with urologic diseases. In 5/21 patients, 250 ml of physiologic saline Solution were injected. In 16/21 patients, 10 mg of furosemide were injected 3-5 min before contrast material administration. A 4 x 2.5 mm collimation with a pitch of 1.25 and a tube current of 100-150 mA were used. Scan time was 12-16 sec. 3 mm thin axial images with an overlap of 67% were reconstructed. Multiplanar maximum intensity projection (MIP) images were postprocessed to obtain urographic views. Bone structures were eliminated using the volume-of-interest method. RESULTS: Furosemide-enhanced MS-CTU achieved either near complete or complete opacification in 30/32 (94%) ureters and in 32/32 (100%) pelvicaliceal systems up to a serum creatinine of 150 mumol/l. In our series, only one CTU scan per patient was needed to obtain a diagnostic urogram after 10 min of contrast material injection. Ureteral compression was not necessary. When physiologic saline solution was used instead of furosemide, the radiopacity inside the enhanced pelvicalices was 4-5 times higher and more inhomogeneous. Diuretic-enhanced MS-CTU was more accurate in the depiction of pelvicaliceal details. In combination with furosemide, calculi were well identified inside the opacified urine and were safely differentiated from phleboliths. Postprocessing times of up to 20 minutes were problematic as were contrast-enhanced superimposing bowel loops on MIP images. CONCLUSION: Preliminary results demonstrate a good feasibility of furosemide-enhanced MS-CTU for obtaining detailed visualization of the entire upper urinary tract.

Correlation between behavioral and neuronal activities of toads Bufo bufo (L.) in response to moving configurational prey stimuli.

Common toads are able to distinguish prey objects from predators and behaviorally irrelevant stimuli by their shape and direction of motion. Using computer programs for correlation analysis, the prey-catching activity in response to different moving configurational stimuli was compared with the activity of neurons recorded at different levels of the visual pathway. Among retinal ganglion cells, the class R2 neurons were found to be most sensitive, to moving configurational stimuli. Among neurons recorded from retinal projection fields in the optic tectum and thalamic pretectal region, the tectal T5(2) neurons exhibited configurational selectivity. The output of these neurons showed the best positive correlation with prey-catching when both the neuronal and behavioral activities were compared in response to stripes of different length moving with their axis in, or perpendicular to, the direction of motion.

[Potency-sparing radical perineal prostatectomy]. / Potenzerhaltende radikale perineale Prostatektomie.

We evaluated the results of a unilateral nerve-sparing radical perineal prostatectomy in a prospective study. Thirty patients with histologically confirmed unilateral prostate cancer and adequate erectile function preoperatively underwent a nerve-sparing procedure. The criteria were a PSA of <10 ng/ml, prostate volume of <60 ml, and a Gleason score <7. In 29 patients the procedure was technically feasible. In one patient significant damage to the neurovascular bundle was seen at the end of the procedure. Bilateral tumors were present in 18 patients on final pathology. Positive surgical margins were observed in five patients (pT2: 2/20; pT3: 3/10). After a follow-up of 3-12 months, 15 of 29 patients (51%) reported some erectile function without additional medication. Of 14 patients, 2 had enough rigidity for penetration within 3 months.The short-term results after unilateral nerve-sparing perineal prostatectomy are encouraging. Since the neurovascular bundle can be exposed very well, interposition of sural nerve should be considered.

[Reverse transcriptase polymerase chain reaction and immunocytochemistry of bone marrow aspiration specimen and peripheral blood for detection of microdisseminated prostatic carcinoma. A comparative analysis]. / Reverse Transkriptase-Polymerase-Kettenreaktion und Immunozytochemie an Knochenmarkaspiraten und peripherem Blut zum Nachweis mikrodisseminierter Prostatakarzinome. Eine vergleichende Analyse.

Reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen and immunocytochemistry for cytokeratin-18 (CK-18) are tests for the detection of microdisseminated carcinoma of the prostate. Bone marrow aspirates and peripheral venous blood from 50 patients with clinically organ-confined prostate cancer were examined. The rate of positive results was independent of the pT stage, serum PSA, and previous antiandrogen treatment. RT-PCR and immunocytochemistry have to be tested under standardized conditions in prospective trials, and the results have to be compared to the serum PSA follow-up.